The putative human mirror neuron system (MNS) is defined as motor brain regions that respond both when we perform an action, and when we observe similar actions being performed by others. Thus, the motor system may be engaged without overt movement. Rehabilitation of motor function after stroke is often challenging due to poor to absent voluntary movement ability. Methods in stroke rehabilitation that engage the MNS, for example, action observation, may help to rebuild motor function despite impairments by using covert practice as an alternative or complement to voluntary practice during physical therapy. The first component of the proposed study will identify the MNS in participants with stroke and damage to the primary motor or premotor cortex by measuring brain activity during action observation and execution in fMRI. The PIs aim to better understand how stroke and motor deficits affect the MNS, and to assess for common patterns of adaptive functional reorganization of the MNS after stroke. The second component of the proposed study will compare the whole brain response between observation of actions that use the counterpart to the paretic and the non-paretic limb. In the healthy brain, action observation is processed primarily by the MNS to support action understanding and imitation. After stroke, some observed actions may be difficult or impossible for the observer to perform due to motor impairments, and thus may engage a more deliberative processing supported by other multimodal cognitive brain regions commonly referred to as the "mentalizing system." The PIs aim to test the hypotheses that (1) observing actions that use the counterpart to the non-paretic limb engages the MNS;whereas (2) observing actions that use the counterpart to the paretic limb engages the MNS plus the mentalizing system. The PIs aim to better understand the cooperative roles of the MNS and the mentalizing system for imitation and social cognition after stroke. The overall aim of this research program is to inform the development of methods that engage the MNS to promote recovery from stroke, and to identify which patients might benefit most from therapy involving action observation. PUBLIC HEALTH RELEVANCE: The mirror neuron system (MNS) - motor brain regions that respond when we perform an action and when we observe similar actions being performed by others - may be engaged to promote motor recovery after stroke in patients with limited voluntary movement ability. By studying how the brain perceives actions after stroke, we will better understand how to use methods that engage the MNS for stroke rehabilitation, for example, action observation. By asking how the brain perceives actions that use the counterpart to the paretic limb, we will better understand the role of the MNS and the mentalizing system for action perception, imitation, and social cognition.